Project Summary Exercise intolerance is the hallmark symptom in patients with heart failure with preserved ejection fraction. As a consequence, activities of daily living require near maximal effort, resulting in further deconditioning and reduced quality of life. While the exact mechanism for the exercise intolerance remains unclear, emerging evidence from our group and others, suggests that impairments in skeletal muscle oxygen delivery and utilization contribute significantly. However, no study to date has simultaneously measured skeletal muscle blood flow and oxidative metabolism in a single subject; making it difficult to assign causality or priority. Broadband near-infrared diffuse correlation spectroscopy (bbNIRS/DCS) has the potential to address this specific limitation, by simultaneously assessing skeletal muscle microvascular perfusion, oxygenation, and mitochondrial function in a single non- invasive imaging session. We are therefore seeking funding to construct and validate a bbNIRS/DCS hybrid system to quantify skeletal muscle perfusion and metabolic function in vivo. Once established, we will extend this novel technology to patients with HFpEF, in order to define specific mechanisms contributing to impaired peripheral oxygen utilization. Together, these studies will not only establish one of the most comprehensive imaging tools for assessing peripheral oxygen delivery and utilization, but will also provide new mechanistic insight into peripheral limitations to exercise in HFpEF.